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Treatment With mTOR Inhibitors as Primary Immunosuppression After Combined Heart and Kidney Transplantation

Hilmi Alnsasra1, Rabea Asleh2, Fouad Khalil3

  • 1Department of Cardiovascular Diseases and Health Sciences Research and the William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota; Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel; Department of Cardiology, Soroka University Medical Center, Beersheva, Israel.

Journal of Cardiac Failure
|December 9, 2024
PubMed
Abstract

Insights

Converting to sirolimus (SRL) after heart or combined heart and kidney transplantation (HKT) effectively reduces death and cardiac allograft vasculopathy (CAV) events. This immunosuppression strategy benefits both heart-only and HKT recipients.

Area of Science:

  • Immunosuppression strategies in organ transplantation
  • Cardiovascular research
  • Nephrology and renal function

Background:

  • Sirolimus (SRL) is known to mitigate cardiac allograft vasculopathy (CAV) and protect renal function post-heart transplantation (HT).
  • The efficacy and safety of SRL in combined heart and kidney transplantation (HKT) remain under investigation.
  • Understanding SRL's impact in HKT versus HT-only is crucial for optimizing immunosuppressive protocols.

Purpose of the Study:

  • To evaluate the impact of converting from calcineurin inhibitors (CNIs) to SRL on CAV progression.
  • To assess renal function and clinical outcomes in HKT recipients compared to HT-only recipients.
  • To determine the safety and efficacy of SRL as a primary immunosuppressant in HKT versus HT.

Main Methods:

  • A cohort of 302 patients (262 HT, 40 HKT) was analyzed.
  • CAV progression was assessed using coronary intravascular ultrasound (IVUS) to measure changes in plaque volume (PV) and plaque index (PI).
  • Patients were converted from CNIs to SRL, with outcomes including death and CAV-related events.

Main Results:

  • HKT showed higher plaque volume progression than HT-only, but this was attenuated by SRL conversion.
  • Conversion to SRL was associated with a reduced risk of death and CAV-related events in the overall cohort.
  • SRL conversion did not significantly impact estimated glomerular filtration rate or proteinuria and showed similar benefits across HT and HKT groups.

Conclusions:

  • Conversion to sirolimus as a primary immunosuppressant is effective for both HT-only and HKT recipients.
  • SRL demonstrates a favorable safety and efficacy profile in managing CAV and improving outcomes in combined transplantation.
  • The study supports the use of SRL in HKT protocols to mitigate CAV progression and reduce adverse clinical events.
Keywords:
Cardiac allograft vasculopathyheart transplantationkidney transplantationmTOR inhibitorsoutcomesirolimus

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